The renin and isorenin-angiotensin system in rats with hereditary hypothalamic diabetes insipidus

It is known that the active end product of the renin-angiotensin system, angiotensin II, will stimulate ADH release in the brain and corticosteroid release from the adrenal gland and it is possible that isorenin-angiotensin systems present in those tissues are important control mechanisms for that release. In these experiments plasma renin and adrenal gland and brain isorenin concentration (ISO-RC) measurements were made in rats of the Brattleboro strain with hereditary hypothalamic diabetes insipidus (DI) both with and without ADH substitution. Heterozygous DI rats have low storage levels of ADH but can maintain normal water balance. These animals had normal plasma renin concentrations and increased ISO-RC in the hypothalamus and neurohypophysis compared to Long-Evans control rats. Substitution with 100 mU ADH/day, given subcutaneously, decreased ISO-RC in both hypothalamic and neurohypophyseal tissues of heterozygous DI to control levels. In comparison with Long-Evans control rats, higher plasma renin concentrations and increased ISO-RC were found in adrenal gland and brain hypothalamus tissue of homozygous DI rats while no differences were observed in frontal cortex, medulla oblongata or choroid plexus. Substitution of homozygous DI rats with 100 mU ADH/day decreased plasma renin concentration but resulted in no correction of adrenal gland or brain ISO-RC. These results suggest the plasma renin-angiotensin system is altered by changes in fluid balance in the DI rat which can be corrected by ADH substitution. Changes in tissue ISO-RC in DI compared to controls are not related to fluid balance but may be correlated with brain ADH content.